Endocrine Abstracts

Pheochromocytoma can present as a sporadic or familial tumor. Classic syndromes include multiple endocrine neoplasia type 2 caused by mutations of the RET gene, Von Hippel-Lindau disease by mutations of the VHL gene and neurofibromatosis by mutations of the NF 1 gene. In 2000 for familial neck paraganglioma the susceptibility gene of succinatedehydrogenasis subunit D, SDHD was identified and subsequently also shown to be mutated in a subset of familial and sporadic pheochromocytoma. This disease is now called paraganglioma syndrome type 1 (PGL 1). Soon afterwards the gene of subunit B (SDHB) was shown to be mutated in an additional subset of pheochromocytomas and paragangliomas (PGL 4) and SDHC in a few neck paraganglioma patients (PGL 3). Different approaches to pheochromocytomas and paragangliomas resulted in a frequency of 24% to 58% of germline mutation carriers of VHL, RET, SDHB, SDHC, and SDHD. Single tumors and lack of family history do not preclude such germline mutations. Mutation carriers of each of the genes have incomplete penetrance. SDHD mutation carriership underlies maternal imprinting, e.g. PGL 1 associated lesions develop only, if the mutation is transmitted by the father. Among phenotype differences, a high (30-50%) proportion of malignant tumors in SDHB mutation carriers dominates. In contrast to SDHB, carriers of SDHD mutations have statistically more frequent head and neck paragangliomas and multifocal tumors. For clinical screening of patients with PGLs, MRI of the neck and skull base, the thorax and the abdomen and measurement of catecholamines in 24hour urine or plasma have to be recommended. This should be supplemented by 18fluoro-dopamin- or DOPA-positron-emission-tomography (PET). Treatment should preferably use minimal invasive and organ sparing surgical techniques. Guidelines for follo-up are pending.